Showing papers on "Lead acetate published in 2004"

Combined efficacies of lipoic acid and 2,3-dimercaptosuccinic acid against lead-induced lipid peroxidation in rat liver

Abstract: Oxidative stress with subsequent lipid peroxidation has been postulated as one mechanism for lead toxicity. Hence in assessing the protective effects of lipoic acid (LA) and meso 2,3-dimercaptosuccinic acid (DMSA) on lead toxicity, they were tested either separately or in combination for their effects on selected indices of hepatic oxidative stress. Elevated levels of lipid peroxides were accompanied by altered antioxidant defense systems. Lead acetate (Pb - 0.2%) was administered in drinking water for five weeks to induce toxicity. LA (25 mg kg−1 body wt. day−1 i.p) and DMSA (20 mg kg−1 body wt. day−1 i.p) were administered individually and also in combination during the sixth week. Lead damage to the liver was evident in the decreases in hepatic enzymes alanine transaminase (−38%), aspartate transaminase (−42%) and alkaline phosphatase (−43%); increases in lipid peroxidation (+38%); decreases in the antioxidant enzymes catalase (−45%), superoxide dismutase (−40%), glutathione peroxidase (−46%) and decreases in glutathione (−43%) and decreases in glutathione metabolizing enzymes, glutathione reductase (−59%), glucose-6-phosphate dehydrogenase (−27%) and glutathione-S-transferase (−42%). In combination LA and DMSA completely ameliorated the lead induced oxidative damage. Either compound alone was however only partially protective against lead damage.

Chemical speciation and cellular deposition of lead in Sesbania drummondii

Abstract: The internalized speciation of lead in roots and leaves of Sesbania drummondii, a lead hyperaccumulator, grown in lead nitrate solution was studied using x-ray absorption near-edge structure and extended x-ray absorption fine structure. Lead was predominantly present as lead acetate in both plant tissues. The other dominant forms of accumulation were lead-sulfur compounds. Whereas lead sulfate and sulfide were found in leaves, only lead sulfide was detected in root samples. These observations indicate that S. drummondii is able to biotransform lead nitrate in the nutrient solution to lead acetate and sulfate in its tissues. Complexation with acetate and sulfate may be a lead detoxification strategy in this plant. Transmission-electron microscopy revealed the pattern of lead distribution in and around the cells. Dense distributions of lead grains were detected in root cell walls and plasma membranes, whereas evidence for vacuolar transport of lead was noticed in the stem cells.

N-acetylcysteine exposure on lead-induced lipid peroxidative damage and oxidative defense system in brain regions of rats.

Abstract: Lead (Pb) is known to disrupt the pro-oxidant/antioxidant balance of tissues, which leads to biochemical and physiological dysfunction. Oxidative stress is considered a possible molecular mechanism involved in Pb neurotoxicity. Considering the vulnerability of the brain to oxidative stress under Pb neurotoxicity, this study investigated the effects of exposure of the thiol antioxidant N-acetylcysteine (NAC) on lead-induced oxidative damage and lipid peroxidation in brain regions of the rat. Wister strain rats were exposed to lead in the form of lead acetate (20 mg/kg body wt/d) for a period of 2 wk and the effects of NAC on lead-induced neurotoxicity in rat brain regions were assessed by postadministration of NAC (160 mg/kg body wt/d) for a period of 3 wk. The lipid peroxidation byproduct, malondialdehyde (MDA) increased following lead exposure in both of the regions, and the antioxidant capacities of the cell in terms of the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was diminished. Following NAC treatment, lead-induced lipid peroxidation decreased and antioxidant enzyme activities improved, with CAT showing enhancement in the cerebral region only and SOD showing enhancements in the cerebellar region. Our result suggests that thiol-antioxidant supplementation following Pb exposure might enhance the reductive status of brain regions by arresting the lipid peroxidative damage in brain regions.

Effect of antioxidant ascorbic acid, l-methionine on tocopherol alone or along with chelator on cardiac tissue of lead-treated rats

Abstract: An experiment was conducted using 42 IVRI 2CQ rats to evaluate the effects of three antioxidants, ascorbic acid, l methionine or α tocopherol alone, or chelator CaNa 2 EDTA alone or along with antioxidant α tocopherol, on lead accumulation, status of lipid peroxidation, and of copper and zinc concentration in cardiac tissue of lead-treated rats. Lead was given intraperitoneally as 1% lead acetate solution at the dose rate of 1mg of Pb2+/kg body mass for a period of 30 days. The lead was then withdrawn and the lead-exposed rats (n=36) were randomly divided into six groups, six lead-treated rats in each group. A further six rats were given no treatment, including lead exposure, to serve as negative controls. The rats were sacrificed under light anaesthesia one day after one week of treatment with antioxidant ascorbic acid, l-methionine or α tocopherol or with chelator CaNa2EDTA alone or along with antioxidant α tocopherol. Blood samples were collected and heart was quickly excised. Mean lead concentration in cardiac tissue was significantly higher in the lead-treated group, even after its withdrawal for a period of seven days (5.02 ± 1.06 vs. 0.40 ± 0.09 µg/gm). The treatment with chelator plus antioxidant α tocopherol lowered the cardiac lead burden but the level remained significantly higher than that of the negative control. There was a non-significant increase in lipid peroxide levels in the cardiac tissue of lead-exposed untreated rats and either of the antioxidants lowered the lipid peroxide level, but the differences between the different treatment groups remained statistically comparable at P>0.05. The mean concentration of copper and zinc in cardiac tissue remained statistically comparable among the different treatment groups.

Effect of simultaneous exposure to lead and cadmium on gonadotropin binding and steroidogenesis on granulosa cells: an in vitro study.

Abstract: Effects of lead (Pb) and cadmium (Cd) both alone or in combination on the binding of LH and FSH on isolated granulosa cells were studied. Granulosa cell s isolated from proestro us rats were incubated (in vitro) with lead acetate and I or cadmium acetate (0.03 !J.M of Pb or Cd) for I hr. LH binding was dropped to 84% in Pb treated cells, 72.5% in Cd treated cell s and 74.8% in combin ed meta l treated cell s compared to control. FSH binding dropped to 85.5 % in Pb treated cell s, 71.16% in Cd treated cell s and 72.5 % in combined metal treated cells compared to control. Activity of 17~ Hydroxy Steroid Dehydrogenase ( 17~HSDH ), a key steroidogenic enzy me was reduced by 52% in Cd and 37% in combined metal exposed cells whereas Pb exposed cells showed 3 1% reduction in the enzy me activity. Pretreatment with SH groups protectant s (glutathione [GSH], dithiothretol fDTT]) and zin c caused an ameriolation in enzyme activity whereas Zn pretreatment showed an increase in gonadotropin binding in metal exposed cell s. These results suggest that both Pb and Cd can cause a reduction in LH and FSH binding, which significantly alters steroid production in vitro and exerts a direct influence on granulosa cell function.

Effect of lead on male gonadal activity in albino rats.

Abstract: Lead poisoning often prevails in children and industrial workers. The present study was undertaken to evaluate the effects of lead acetate on steroidogenic functions of testis, serum levels of gonadotrophins and testosterone in albino rats. Testicular steroidogenic activity was evaluated by measuring the activities of two steroidogenic key enzymes, ∆ 5 –3β hydroxysteroid dehydrogenase (∆ 5 –3β–HSD) and 17β–hydroxysteroid dehydrogenase (17β–HSD). Administration of lead acetate at a dose of 8mg/kg body weight for 14 days lowered the weights of testes and accessory sex organs, and decreased testicular ∆ 5 –3β – HSD and 17β– HSD activities and serum levels of FSH, LH and testosterone but 7 days of lead acetate administration showed no effect on the above parameters. This report is perhaps the first evidence to show that lead exerts some deleterious effects on testicular steroidogenesis indirectly by decreasing serum levels of gonadotropins.

Developmental Immunotoxicity of Lead in the Rat: Influence of Maternal Diet

Abstract: The effect of maternal dietary protein intake on lead-induced developmental immunotoxicity was studied in female Fischer 344 rats receiving lead acetate (250 ppm) or sodium acetate (control) in the drinking water during breeding and pregnancy until parturition. Dams were fed isocaloric diets (either 20% casein or 10% casein) from 2 wk prior to mating until the end of lactation. After weaning, dams and female offspring were given the 20% casein diet and regular water. Immune function was assessed in dams at 8 wk postpartum and in offspring at 13 wk of age. Dams showed no marked difference in any of the immune endpoints examined, regardless of diet or lead treatment. In contrast, lead exposure during early development produced a subsequent significant reduction of both the delayed-type hypersensitivity response and interferon γ production in adult offspring independent of maternal diet. Lead-exposed offspring from the high-dietary-protein group had significantly elevated production of both interleukin-4 and...

Succimer treatment and calcium supplementation reduce tissue lead in suckling rats.

Abstract: The effect of combined treatment with meso-2,3-dimercaptosuccinic acid (DMSA) and calcium supplementation in reducing lead absorption and enhancing lead elimination was evaluated in suckling rats under two experimental conditions: during ongoing oral lead exposure (lead acetate, 2 mg Pb kg−1 day−1, total dose 16 mg Pb kg−1) or after lead exposure (72 h after a 2-day lead exposure, total dose 12 mg Pb kg−1 s.c.). The artificial feeding method was used for calcium supplementation, with 6% Ca (as CaHPO4) suspension in cow's milk to increase the daily calcium intake about three times above control values. Artificial feeding lasted for 7 h a day over eight consecutive days. During this period DMSA was administered on 6 days twice a day (0.5 mmol kg−1 day−1 p.o.). At the end of the experiments, Pb, Ca and Zn in the carcass and Pb, Fe and Cu in the liver, kidneys and brain were analysed by atomic absorption spectrometry. Calcium supplementation during lead exposure reduced tissue lead but had no effect when applied after lead exposure, and DMSA administered either during or after lead exposure lowered the tissue lead. Combined treatment during ongoing lead exposure caused a greater reduction in tissue lead than either DMSA or calcium treatment alone. When administered after lead exposure, it had no advantage over DMSA treatment alone but did not impair its efficacy. Combined treatment had no influence on growth and did not seriously disturb essential element status. It is concluded that calcium supplementation could be applied during DMSA therapy, when indicated. Copyright © 2004 John Wiley & Sons, Ltd.

Lead acetate genotoxicity in suckling rats

Abstract: The mutagenic and carcinogenic potentials of lead are still being investigated. The aim of this study was to evaluate the genotoxic effect of lead acetate in the early period of life, when the organism is extremely sensitive to toxic effects of lead. Six-day-old suckling Wistar rats were exposed to lead (as acetate) either orally for 9 days (daily dose 2 mg Pb/kg b. wt., 18 mg/kg b.wt. total dose) or by a single intraperitoneal injection (5 mg Pb/kg b. wt.). DNA damage was investigated using the comet assay and in vivo micronucleus test. The results of the comet assay showed statistically significant differences between the control (unexposed) animals and the two groups of exposed animals by ANOVA weighted for unequal variance (heterogeneity of variances was found by Levene’s test), followed by Tukey’s post hoc test at the level of significance of p< 0.05. The two groups of lead-exposed animals were also significantly different from each other. Orally lead-exposed animals showed a significant increase of micronuclei frequencies in reticulocytes and erythrocytes compared to unexposed animals (ANOVA, p< 0.05).

Altered cytokine production in mice exposed to lead acetate.

Abstract: Previous investigations have shown that Pb exerts immunotoxic effects. Object of this study were Th1 and Th2-type immune responses of mice to Pb exposure. Adult Swiss male mice were administered 0, 40 and 400 mg/l of Pb (as acetate) in drinking water for 14 days. At the end of the treatment, blood Pb was determined and two Th1 cytokines (IL-2, INF-gamma) and one Th2 serum cytokine (IL-4) were measured. A significant increase in IL-4 production was observed in the mice exposed to 40 mg/l of Pb, while a further increase in IL-4 production was associated with a decrease in INF-gamma production in mice exposed to 400 mg/l of Pb. On the other hand, Pb exposure did not induce changes of serum IL-2 (involved also in the Th0 immune pattern). Our findings indicate that low level Pb exposure enhances a Th2 response. A high Pb does can either stimulate the Th2 immune activity or reduce the Th1 response; the result is an imbalance between Th1 and Th2 activation.

Inorganic Lead Exposure in the Rat Activates Striatal cFOS Expression at Lower Blood Levels and Inhibits Amphetamine-Induced cFOS Expression at Higher Blood Levels

Abstract: The impact of inorganic lead exposure on dopamine (DA) neurotransmission in the basal ganglia was examined. Amphetamine (AMPH)-induced cFOS immunoreactivity (cFOS-IR) in the striatum was determined after a 3-week exposure to lead acetate (0, 50, or 250 ppm). On the 21st day of lead exposure, rats were challenged with AMPH (4 mg/kg i.p.) or saline vehicle (Veh) and were assayed for presence of cFOS-IR. In the untreated control (Con) group, AMPH challenge (Con/AMPH) increased cFOS-IR expression by approximately 35-fold over Veh challenge (Con/Veh) (P 0.20). Neither the Pb250/Veh group nor the Pb250/AMPH group had a significant increase in cFOS-IR relative to Con/Veh (P > 0.20). These results indicate that chronic 50 ppm lead exposure induced a low but statistically significantly level of cFOS gene activation and that it did not affect the AMPH-induced cFOS activation. However, chronic 250 ppm lead exposure inhibited AMPH-induced activation of cFOS in the striatum by about 89%. Therefore, lead is capable of both activating cFOS expression at low levels of exposure (mean blood lead level 21.6 +/- 1.9 microg/dl) and inhibiting AMPH-induced cFOS expression at higher levels of exposure (mean blood lead level 47.4 +/- 2.6 microg/dl).

Lead induced modulation of splenic macrophage responses on humoral and cell mediated immunity.

Abstract: The heavy metal lead is an environmental toxic material that can induce pathophysiological changes in many organ systems. Previous studies have shown the effects of lead exposure on immune cells in different experimental animals, however, the mechanism of their influence on the immune system is unclear. We reported that in vivo lead exposure inhibits phagocytosis, nitric oxide release, induces DNA fragmentation suggesting the apoptotic death of the target cell. We have also presented evidence that inhibition of macrophage functional responses implicated alteration of humoral and cell mediated immunity. In vivo exposure to lead acetate alters the phagocytic capacity of splenic macrophages as evident from the reduction of phagocytic index of control from 19,792+/-1385.69 to 8893+/-893 in the treated group. The amount of nitric oxide released by the control cell 2.25+/-0.125 microM is also reduced to 1.9375+/-0.0625 microM upon in vivo lead treatment. Functional integrity of the target cell is also decreased after lead exposure as obtained from the percentage of DNA fragmentation. Control group shows 33.29+/-0.11% of fragmented DNA, which is enhanced to 42.43+/-0.725% following the lead treatment. A greater percentage of DNA fragmentation upon lead treatment probably indicating that the heavy metal induces apoptosis. The humoral immune response is also altered after lead exposure as indicated by the decrease of the antibody titre in control group from 1:2048 to 1:128 in the treated group. From the DTH reaction, it was observed that the mean diameter of swollen foot pad of control mice is 0.329+/-0.15 cm and that of lead treated mice is 0.274+/-0.056 cm. It can, therefore, be suggested that lead inhibits normal functional activities of splenic leukocytes, particularly phagocytosis and also affects the functional integrity of cells by inducing DNA fragmentation. The study may demonstrate the usefulness of investigation of humoral immune system and leukocyte functions as sensitive parameters in detecting the effects of lead toxicity.

Study of effects of lead acetate on reproductive function in male mice

Abstract: Male mice were orally administered with lead acetate of10mg/kg,20mg/kg and40mg/kg,respectively,via gastric tube once daily for35days,consecutively.Activities of glucose-6-phosphate dehydrogenase(G-6-PD),acid phosphatase(ACP),β-glycosidase(β-G),lactic acid dehydrogenase(LDH)and lactic acid dehydrogenase isoenzyme(LDHx)in the serum and testis ho-mogenate of male mice were determined with spectrophotometry and their fertility was measured with a standard method.Their testis and epididymis were examined histopathologically.Results showed that insemination rate in male mice,pregnancy rate in female mice,av-erage number of live birth of mice per nest and activities ofβ-G and LDHx in testis homogenate decreased with the increase of dose of lead acetate,as compared to the control mice,while stillbirth rate and embryo resorption rate increased with dose of lead acetate,in a significant dose-response pattern,as compared with the negative control group(P0.05),with coefficients of regression of-0.412,-0.420,-0.537,-0.538,-0.617,0.542and0.535,respectively.While,mating rate in male mice,activities of G-6-PD,ACP and LDH in the serum and testis homogenate in the rats exposed to40mg/kg of lead acetate were significantly different from those in the negative control group(P0.01or P0.05),indicating that fertility in male mice could be damaged by exposed to≥20mg/kg of lead acetate.

[Effects of lead on the Brn-3a expression and the apoptosis in hippocampus neurons].

Abstract: OBJECTIVE Explore the effects of lead on the expression of Brn-3a transcription factor and the induction of apoptosis in vitro. METHODS Experiment cell model was established using primary culture of hippocampus neurons of SD rat embryos. Target cells were exposed to lead acetate with the different concentration, i.e. 0.1, 1, 10, 100, 1000 mumol/L, whilst the control group was given the same quantity of the culture medium. The survival rate was determined 24 h and 48 h after exposure by MTT method. Brn-3a expression and apoptosis induction were investigated by means of immuno-histochemistry and TUNEL methods respectively. RESULTS 1 mumol/L lead acetate treatment significantly decreased the IOD of Brn-3a positive neurons (P < 0.05) and 10 mumol/L caused a marked decline of the rate of positive area (P < 0.01) compared with the control group. In addition, 1 mumol/L lead acetate was demonstrated to be the minimal concentration to induce apoptosis of cultured hippocampus neurons with a dose response effects found in higher concentrations. CONCLUSION It is indicated that the impairments of hippocampus caused by lead was at least partly related to the apoptosis induction by lead. Furthermore, decrease of Brn-3a expression followed by lead treatment might be probably one of the mechanisms to the apoptosis induced by lead in hippocampus.

"the protective role of l-cysteine against follicular atresia induced by lead in mouse ovary"

Abstract: Lead is an ubiquitous environmental toxin that induces a broad range of physiological biochemical, and behavioral dysfunctions. In this study, we examined the pathologic effects of lead acetate in NMRI mouse ovarian tissue and the protective role of antioxidant L-cysteine, against the induced damage. We used lead acetate at a dose of 10 mg/kg, and L-cysteine at a dose of 200 mg/kg. Both drugs were administered intraperitoneally according to 2 protocols: intraperitoneal injection of lead acetate 10 mg/kg/day for 15 days or 10 mg/kg/week for 15 weeks. Ovaries were examined histologically and changes in the number of graafian, growing, atretic, and primordial follicles, thickness of granolusa of theca layers, relative ovary weight (ROW) and animal weights, were determined. Significantly increased numbers of atretic follicles and thickness of the theca layer, and a decrease in other parameters were observed after treatment with lead acetate (P< 0.05). No changes were observed after treatment with a combination of L-cysteine. Also, more oocytes had resumed meiosis in the follicles exposed to lead acetate. The results suggest that lead acetate at a dose of 10 mg/kg has a toxic effect on ovarian tissue, and antioxidants such as L-cysteine have a protective role against the induced damage.